P14.23 Different in Situ Immune Pattern Between Primary Tumor and Metastatic Lymph Node in NSCLC: Potential Impact on Neoadjuvant Immunotherapy

Abstract

Neoadjuvant immunotherapy is now preferred for locally-advanced non-small cell lung cancer (NSCLC). The in situ immune pattern, as potential predictor of PD-1/PD-L1 blockade outcomes, of the primary tumor (PT) and metastatic lymph nodes (mLNs) of NSCLC is unknown. Multiplex immunofluorescence staining and multispectral imaging were used to evaluate the in situ immune pattern of T cells (CD3+) and cytotoxic T cells (CD8+) in terms of density and location (center of tumor [CT] and invasive margin [IM]) and the PD-L1 expression status of tumor cells and stromal T cells of paired PTs and mLNs in 38 stage III NSCLCs. The densities of T cells and cytotoxic T cells were correlated between PTs and mLNs at both CT and IM. Higher densities of stromal T cells (S-CD3+) at CT and both S-CD3+ and cytotoxic T cells (S-CD8+) at IM were observed in mLNs compared to PTs, while in tumor compartment, there were no differences in the densities of T cells (T-CD3+) or cytotoxic T cells (T-CD8+). Only the density of stromal PD-L1-positive T cells (S-PD-L1+CD3+) at CT was correlated between PTs and mLNs, while the densities and frequencies of S-PD-L1+CD3+ at CT and IM of mLNs were higher than PTs. The difference in the combine positive score of PD-L1 between PTs and mLNs was greater than that in the tumor proportion score. The results may further interpret a better immune-mediated pathologic response in mLNs, as a case of stage III (N2) NSCLC who received neoadjuvant chemo-immunotherapy experienced pathologic complete remission of his mediastinal lymph node but only partial remission of the primary tumor. Figure 1. Multiplex immunofluorescence staining and multispectral imaging to visualize the expression of CD3, CD8, PD-L1 and cytokeratin (CK) in primary tumors (PTs) and metastatic lymph nodes (mLNs). Higher densities of CD3+ and CD8+ were observed in stroma compartment compared to tumor compartment in both PT and mLN. The in situ immune patterns of T cells and cytotoxic T cells were different between PTs and mLNs in NSCLC. Higher densities of S-CD3+ and S-PD-L1+CD3+ in mLNs may resulted in a better immune-mediated pathologic response to neoadjuvant immunotherapy.